Patients with hepatitis B showed continued improvement in bone safety after 2 years of treatment with tenofovir alafenamide compared with tenofovir disoproxil fumarate, according to a recently published study.
According to Wai-Kay Seto, MD, from the University of Hong Kong, and colleagues, tenofovir alafenamide (TAF) is more stable in plasma compared with tenofovir disoproxil fumarate (TDF), which enables more efficient delivery of the active form of tenofovir disphosphate to hepatocytes at a lower dose than TDF is traditionally prescribed.
“While TDF is highly efficacious monotherapy for [chronic HBV (CHB)], its use is associated with osteopenia and [bone mineral density (BMD)] loss,” Seto and colleagues wrote. “As the population of CHB patients requiring lifelong therapy ages, the potential exists for the long-term safety advantages of TAF therapy relative to TDF to be more fully realized.”
Seto and colleagues randomly assigned 1,298 patients with HBV to receive either TAF 25 mg (n = 866) or TDF 300 mg (n = 432) once daily for 96 to 144 weeks. The overall cohort included patients who were either HBV e antigen positive (n = 873) or negative (n = 425) and either treatment experienced or treatment naive.
Mean decrease in hip BMD was significantly less among the TAF group compared with the TDF group at week 48 (–0.16% vs. –1.86%; P < .001) and at week 96 (–0.33% vs. –2.51%; P < .001). Similarly, mean decrease in spine BMD was less in the TAF group at week 48 (–0.57% vs. –2.37%; P < .001) and week 96 (–0.75% vs. –2.57%; P < .001).
Among patients with higher risk for bone loss, the researchers observed a smaller proportion of patients who experienced a bone loss of more than 3% in hip BMD in the TAF group compared with the TDF group by subanalysis of risk factors including female sex (18% vs. 50%; P < .001), advanced age (20% vs. 52%; P < .001), Asian ethnicity (15% vs. 42%; P < .001) and baseline renal impairment (20% vs. 54%; P < .001). Results were similar for spine BMD changes.
Independent predictors for a decrease in hip BMD included TAF vs. TDF treatment (OR = 0.232; 95% CI, 0.17-0.317), no prior use of interferons (OR = 0.462; 95% CI, 0.295-0.723), age younger than 50 years vs. 50 years (OR = 0.619; 95% CI, 0.43-0.889), female vs. male sex (OR = 1.471; 95% CI, 1.065-2.032) and baseline renal impairment (OR = 0.991; 95% CI, 0.984-0.998).
“Taken together, our results support the concept that reduced systemic exposures of tenofovir may be responsible for the minimal changes in bone turnover and smaller declines in BMD observed in patients receiving TAF vs. those receiving TDF,” the researchers concluded. – by Talitha Bennett
Disclosure: Seto reports advisory or speaker positions with AbbVie, Bristol-Myers Squibb and Gilead. Please see the full study for the other authors’ relevant financial disclosures